{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:44:30Z","timestamp":1793508270943,"version":"4.5.0"},"reference-count":47,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"1","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>MRI-guided low-intensity focused ultrasound (FUS) has been shown to reversibly open the blood-brain barrier (BBB), with the potential to deliver therapeutic agents noninvasively to target brain regions in patients with Alzheimer\u2019s disease (AD) and other neurodegenerative conditions. Previously, the authors reported the short-term safety and feasibility of FUS BBB opening of the hippocampus and entorhinal cortex (EC) in patients with AD. Given the need to treat larger brain regions beyond the hippocampus and EC, brain volumes and locations treated with FUS have now expanded. To evaluate any potential adverse consequences of BBB opening on disease progression, the authors report safety, imaging, and clinical outcomes among participants with mild AD at 6\u201312 months after FUS treatment targeted to the hippocampus, frontal lobe, and parietal lobe.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In this open-label trial, participants with mild AD underwent MRI-guided FUS sonication to open the BBB in \u03b2-amyloid positive regions of the hippocampus, EC, frontal lobe, and parietal lobe. Participants underwent 3 separate FUS treatment sessions performed 2 weeks apart. Outcome assessments included safety, imaging, neurological, cognitive, and florbetaben \u03b2-amyloid PET.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Ten participants (range 55\u201376 years old) completed 30 separate FUS treatments at 2 participating institutions, with 6\u201312 months of follow-up. All participants had immediate BBB opening after FUS and BBB closure within 24\u201348 hours. All FUS treatments were well tolerated, with no serious adverse events related to the procedure. All 10 participants had a minimum of 6 months of follow-up, and 7 participants had a follow-up out to 1 year. Changes in the Alzheimer\u2019s Disease Assessment Scale\u2013cognitive and Mini-Mental State Examination scores were comparable to those in controls from the Alzheimer\u2019s Disease Neuroimaging Initiative. PET scans demonstrated an average \u03b2-amyloid plaque of 14% in the Centiloid scale in the FUS-treated regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>This study is the largest cohort of participants with mild AD who received FUS treatment, and has the longest follow-up to date. Safety was demonstrated in conjunction with reversible and repeated BBB opening in multiple cortical and deep brain locations, with a concomitant reduction of \u03b2-amyloid. There was no apparent cognitive worsening beyond expectations up to 1 year after FUS treatment, suggesting that the BBB opening treatment in multiple brain regions did not adversely influence AD progression. Further studies are needed to determine the clinical significance of these findings. FUS offers a unique opportunity to decrease amyloid plaque burden as well as the potential to deliver targeted therapeutics to multiple brain regions in patients with neurodegenerative disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3171\/2022.9.jns221565","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T19:00:52Z","timestamp":1667588452000},"page":"275-283","source":"Crossref","is-referenced-by-count":101,"title":["Focused ultrasound\u2013mediated blood-brain barrier opening in Alzheimer\u2019s disease: long-term safety, imaging, and cognitive outcomes"],"prefix":"10.3171","volume":"139","author":[{"given":"Ali R.","family":"Rezai","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery,"},{"name":"Neurosciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Ranjan","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc W.","family":"Haut","sequence":"additional","affiliation":[{"name":"Behavioral Medicine and Psychiatry,"},{"name":"Neurology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Neuroradiology, WVU Rockefeller Neuroscience Institute, Morgantown, West Virginia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Fran\u00e7ois","family":"D\u2019Haese","sequence":"additional","affiliation":[{"name":"Neuroradiology, WVU Rockefeller Neuroscience Institute, Morgantown, West Virginia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashi I.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Neuroradiology, WVU Rockefeller Neuroscience Institute, Morgantown, West Virginia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umer","family":"Najib","sequence":"additional","affiliation":[{"name":"Neurology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Neuroradiology, WVU Rockefeller Neuroscience Institute, Morgantown, West Virginia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel O.","family":"Claassen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University, Nashville, Tennessee;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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